Hematopoietic differentiation of embryonic stem cells: a model to study the biology of hematopoiesis.

The manipulation of embryonic stem (ES) cells allows to generate mice with specific alteration in any gene. This is therefore an unvaluable tool for studying gene function. A number of genes involved in the regulation of hematopoiesis have been inactivated, including genes that encode transcription factors, cytokines and their receptors as well as those encoding for intracellular signalling proteins. Alternatively, ES cells are able to differentiate towards myeloid, lymphoid and endothelial lineages under specific culture conditions. The role of master genes controlling hematopoiesis can be investigated by substituting the in vitro hematopoietic differentiation model of ES cells to mice fabrication. This method can be applied for studying effects of gene inactivation or overexpression of normal or abnormal gene. interestingly, in vitro differentiation of ES cells recapitulates some aspects of embryonic development, including the emergence of the hemangioblast, the common precursor of hematopoietic and endothelial lineages. Thus, hematopoietic differentiation of ES cells constitutes a model far studying effects of gene manipulation on both hematopoiesis and emergence and commitment of the more hematopoietic primitive cell, the hemangioblast, during embryogenesis. In our studies, we used ES cells inactivated for the c-mpl gene, the thrombopoietin receptor, for dissecting the functions of various intracytoplasmic domain of c-mpl in the response of ES cell-derived hematopoietic cells to TP0. (C) 2001 Editions scientifiques et medicales Elsevier SAS.